Francesco Claps1,2, Maaike W van de Kamp1, Roman Mayr3, Peter J Bostrom4,5, Joost L Boormans6, Markus Eckstein7, Laura S Mertens1, Egbert R Boevé8, Yann Neuzillet1,9, Maximilian Burger3, Damien Pouessel9,10, Carlo Trombetta2, Bernd Wullich11, Theo H van der Kwast12, Arndt Hartmann7, Yves Allory9,13, Yair Lotan14, Shahrokh F Shariat14,15,16,17,18, Tahlita C M Zuiverloon6, M Carmen Mir19, Bas W G van Rhijn20,21,22. 1. Department of Surgical Oncology (Urology), Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. 2. Department of Medicine, Surgery and Health Sciences, Urological Clinic, University of Trieste, Trieste, Italy. 3. Department of Urology, Caritas St Josef Medical Center, University of Regensburg, Regensburg, Germany. 4. Department of Surgical Oncology (Urology), Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, ON, Canada. 5. Department of Urology, Turku University Hospital and University of Turku, Turku, Finland. 6. Department of Urology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands. 7. Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen/Nurnberg, Erlangen, Germany. 8. Department of Urology, St Franciscus Hospital, Rotterdam, The Netherlands. 9. Institut Curie, CNRS, UMR144, Molecular Oncology Team, PSL Research University, 75005, Paris, France. 10. Department of Medical Oncology, Claudius Regaud Institute, Toulouse University Cancer Center (IUCT) Oncopole, 31000, Toulouse, France. 11. Department of Urology and Pediatric Urology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen/Nurnberg, Erlangen, Germany. 12. Department of Pathology, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, ON, Canada. 13. Department of Pathology, Institut Curie, 75005, Paris, France. 14. Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA. 15. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. 16. Department of Urology, Weill Cornell Medical College, New York, NY, USA. 17. Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic. 18. Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia. 19. Department of Urology, Fundacion Instituto Valenciano Oncologia, Valencia, Spain. 20. Department of Surgical Oncology (Urology), Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. b.v.rhijn@nki.nl. 21. Department of Urology, Caritas St Josef Medical Center, University of Regensburg, Regensburg, Germany. b.v.rhijn@nki.nl. 22. Department of Surgical Oncology (Urology), Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, ON, Canada. b.v.rhijn@nki.nl.
Abstract
PURPOSE: To evaluate the risk factors associated with positive surgical margins' (PSMs) location and their impact on disease-specific survival (DSS) in patients with bladder cancer (BCa) undergoing radical cystectomy (RC). METHODS: We analyzed a large multi-institutional cohort of patients treated with upfront RC for non-metastatic (cT1-4aN0M0) BCa. Multivariable binomial logistic regression analyses were used to assess the risk of PSMs at RC for each location after adjusting for clinicopathological covariates. The Kaplan-Meier method was used to estimate DSS stratified by margins' status and location. Log-rank statistics and Cox' regression models were used to determine significance. RESULTS: A total of 1058 patients were included and 108 (10.2%) patients had PSMs. PSMs were located at soft-tissue, ureter(s), and urethra in 57 (5.4%), 30 (2.8%) and 21 (2.0%) patients, respectively. At multivariable analysis, soft-tissue PSMs were independently associated with pathological stage T4 (pT4) (Odds ratio (OR) 6.20, p < 0.001) and lymph-node metastases (OR 1.86, p = 0.04). Concomitant carcinoma-in-situ (CIS) was an independent risk factor for ureteric PSMs (OR 6.31, p = 0.003). Finally, urethral PSMs were independently correlated with pT4-stage (OR 5.10, p = 0.01). The estimated 3-years DSS rates were 58.2%, 32.4%, 50.1%, and 40.3% for negative SMs, soft-tissue-, ureteric- and urethral PSMs, respectively (log-rank; p < 0.001). CONCLUSIONS: PSMs' location represents distinct risk factors' patterns. Concomitant CIS was associated with ureteric PSMs. Urethral and soft-tissue PSM showed worse DSS rates. Our results suggest that clinical decision-making paradigms on adjuvant treatment and surveillance might be adapted based on PSM and their location.
PURPOSE: To evaluate the risk factors associated with positive surgical margins' (PSMs) location and their impact on disease-specific survival (DSS) in patients with bladder cancer (BCa) undergoing radical cystectomy (RC). METHODS: We analyzed a large multi-institutional cohort of patients treated with upfront RC for non-metastatic (cT1-4aN0M0) BCa. Multivariable binomial logistic regression analyses were used to assess the risk of PSMs at RC for each location after adjusting for clinicopathological covariates. The Kaplan-Meier method was used to estimate DSS stratified by margins' status and location. Log-rank statistics and Cox' regression models were used to determine significance. RESULTS: A total of 1058 patients were included and 108 (10.2%) patients had PSMs. PSMs were located at soft-tissue, ureter(s), and urethra in 57 (5.4%), 30 (2.8%) and 21 (2.0%) patients, respectively. At multivariable analysis, soft-tissue PSMs were independently associated with pathological stage T4 (pT4) (Odds ratio (OR) 6.20, p < 0.001) and lymph-node metastases (OR 1.86, p = 0.04). Concomitant carcinoma-in-situ (CIS) was an independent risk factor for ureteric PSMs (OR 6.31, p = 0.003). Finally, urethral PSMs were independently correlated with pT4-stage (OR 5.10, p = 0.01). The estimated 3-years DSS rates were 58.2%, 32.4%, 50.1%, and 40.3% for negative SMs, soft-tissue-, ureteric- and urethral PSMs, respectively (log-rank; p < 0.001). CONCLUSIONS: PSMs' location represents distinct risk factors' patterns. Concomitant CIS was associated with ureteric PSMs. Urethral and soft-tissue PSM showed worse DSS rates. Our results suggest that clinical decision-making paradigms on adjuvant treatment and surveillance might be adapted based on PSM and their location.
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